Single-cell RNA sequencing reveals C7+ cancer-associated fibroblasts' role in incomplete resection, suggesting novel therapeutic targets for ovarian cancer.
Background/Objectives: Achieving complete resection (R0) during secondary cytoreduction (SCR) is a pivotal prognostic factor for patients with platinum-sensitive relapsed ovarian cancer (PSROC). Methods: By integrating single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and functional assays on primary cells, we identified tumor microenvironment (TME) heterogeneity, particularly the presence of distinct subpopulations of cancer-associated fibroblasts (CAFs), as a critical determinant of surgical outcomes for SCR. Results: We characterized a previously unrecognized CAF-C7 subpopulation that was selectively enriched in tumors from non-R0 patients. Mechanistically, CAF-C7 promoted tumor cell migration, suppressed anoikis, and facilitated angiogenesis via the IGF1-IGF1R signaling axis, thereby contributing to multifocal recurrence and reducing the likelihood of complete resection. Importantly, the inhibition of the IGF1-IGF1R pathway effectively attenuated the pro-tumorigenic functions of CAF-C7. Conclusions: These findings uncover a novel cellular driver of unfavorable surgical outcomes in PSROC and suggest promising biomarkers and therapeutic targets for improving patient stratification and treatment in the context of SCR.
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Li et al. (2025) studied this question.
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